Abstract
BACKGROUND: The correlation between asthma and frailty is increasingly garnering attention. The association between asthma and frailty remains inconclusive in observational studies, and the causality of this relationship still needs to be established. AIMS: Therefore, we employed two-sample Mendelian randomization analyses using genetic instruments to determine the causal association of asthma on frailty. METHODS: Two-sample Mendelian randomization (MR) analyses were performed to assess the causal effect of asthma on frailty. The genetic variants strongly associated with asthma (P < 5E-08) during the discovery and replication stages were derived from a recent meta-analysis of genome-wide association studies (GWAS) (N = 408,442) in the UK Biobank and a GWAS in the FinnGen Consortium (N = 217,421), respectively. Summary statistics of the frailty index (N = 175,226) are derived from the latest released GWAS dataset on frailty index. The inverse variance weighted (IVW) method was employed as the primary approach for calculating estimated values, with additional sensitivity analyses and heterogeneity analyses utilized to further validate the results. RESULTS: Using the IVW method, genetic susceptibility to asthma was associated with an increased risk of frailty in the discovery stage (odds ratio [OR] = 1.092, 95% confidence interval [CI] = 1.075-1.109, P = 5.00E-28), which was also validated in the replication stage (OR = 1.073, 95% CI = 1.052-1.096, P = 1.41E-11). Sensitivity analyses yielded consistent causal estimate, and no significant pleiotropy was found throughout the MR study. CONCLUSION: The present study demonstrated that asthma is causally associated with an elevated risk of frailty. Further studies are needed to elucidate the potential pathophysiological mechanisms between asthma and frailty.